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MBC in Press, published online ahead of print April 30, 2008
Mol. Biol. Cell 10.1091/mbc.E07-10-1025

A more recent version of this article appeared on July 1, 2008 Originally published as MBC in Press, 10.1091/mbc.E07-10-1025 on April 16, 2008
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Submitted on October 10, 2007
Revised on March 24, 2008
Accepted on April 9, 2008

Glypican-1 Regulates Anaphase Promoting Complex/Cyclosome (APC/C) Substrates and Cell Cycle Progression in Endothelial Cells

Dianhua Qiao,* Xinhai Yang,* Kristy Meyer,* and Andreas Friedl*{dagger}

*Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, WI 53792; {dagger}Pathology and Laboratory Medicine Service, Department of Veterans Affairs Medical Center, Madison, WI 53705

Monitoring Editor: Richard Assoian

Glypican-1 (GPC1), a member of the mammalian glypican family of heparan sulfate proteoglycans, is highly expressed in glioma blood vessel endothelial cells (ECs). In this study, we investigated the role of GPC1 in EC replication by manipulating GPC1 expression in cultured mouse brain ECs. Moderate GPC1 overexpression stimulates EC growth, but proliferation is significantly suppressed when GPC1 expression is either knocked down or the molecule is highly overexpressed. Flow cytometric and biochemical analyses show that high or low expression of GPC1 cause cell cycle arrest at the G2 phase of the cell cycle and/or mitosis, accompanied by endoreduplication and consequently polyploidization. We further show that GPC1 inhibits the anaphase promoting complex/cyclosome (APC/C) mediated degradation of mitotic cyclins and securin. High-levels of GPC1 induce metaphase arrest and centrosome overproduction, alterations which are mimicked by overexpression of cyclin B1 and cyclin A, respectively. These observations suggest that GPC1 regulates EC cell cycle progression at least partially by modulating APC/C mediated degradation of mitotic cyclins and securin.

Address correspondence to: Andreas Friedl (afriedl{at}wisc.edu)






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